Background
Methods
Data source
Study population and exposure determination
Study outcome
Confounders adjustment
Statistical analysis
Results
Patient characteristics prior matching
Patient characteristics before PS matching | DPP-4 inhibitors | GLP-1 agonists | P-value | ||
---|---|---|---|---|---|
(n = 358,632) | (n = 174,711) | ||||
Mean age, years (± SD) | 59.0 | (± 12.1) | 52.9 | (± 10.4) | < 0.001 |
Sex, n (%) | |||||
Male | 196,172 | (54.7) | 75,475 | (43.2) | < 0.001 |
Female | 162,460 | (45.3) | 99,236 | (56.8) | |
Type of DPP-4 inhibitors | |||||
Saxagliptin | 51,233 | (14.3) | NA | – | – |
Sitagliptin | 286,259 | (79.8) | NA | – | – |
Alogliptin | 20,720 | (5.8) | NA | – | – |
Linagliptin | 409 | (0.1) | NA | – | – |
Comorbidities, n (%) | |||||
Asthma | 19,007 | (5.3) | 11,182 | (6.4) | < 0.001 |
COPD | 21,518 | (6.0) | 7163 | (4.1) | < 0.001 |
CKD | 24,028 | (6.7) | 4717 | (2.7) | < 0.001 |
Ischemic heart disease | 64,554 | (18) | 22,188 | (12.7) | < 0.001 |
Depression | 11,835 | (3.3) | 8386 | (4.8) | < 0.001 |
Stroke | 22,235 | (6.2) | 5591 | (3.2) | < 0.001 |
Hypoglycemia | 11,835 | (3.3) | 5765 | (3.3) | 0.320 |
Hyperlipidemia | 196,889 | (54.9) | 95,567 | (54.7) | 0.354 |
Cancer | 35,863 | (10.0) | 11,007 | (6.3) | < 0.001 |
Hypertension | 222,352 | (62.0) | 100,634 | (57.6) | < 0.001 |
Acute myocardial infarction | 5379 | (1.5) | 1223 | (0.7) | < 0.001 |
Heart failurea | 8966 | (2.5) | 1747 | (1.0) | < 0.001 |
Prior cardiovascular diseases | 81,051 | (22.6) | 27,255 | (15.6) | < 0.001 |
Use of other diabetes medications, n (%) | |||||
Metformin | 210,876 | (58.8) | 108,845 | (62.3) | < 0.001 |
TZDs | 94,320 | (26.3) | 48,395 | (27.7) | < 0.001 |
α-Glucosidase inhibitors | 2152 | (0.6) | 1048 | (0.6) | 0.694 |
Insulin | 35,863 | (10.0) | 39,485 | (22.6) | < 0.001 |
Meglitinides | 9683 | (2.7) | 4717 | (2.7) | 0.507 |
Use of other medications, n (%) | |||||
ACE inhibitors | 128,390 | (35.8) | 57,655 | (33.0) | < 0.001 |
Aldosterone receptor antagonists | 8966 | (2.5) | 4542 | (2.6) | 0.047 |
α-Blockers | 24,746 | (6.9) | 7687 | (4.4) | < 0.001 |
Angiotensin-receptor blockers | 56,305 | (15.7) | 26,381 | (15.1) | < 0.001 |
β-Blockers | 104,721 | (29.2) | 40,358 | (23.1) | < 0.001 |
Calcium-channel blockers | 68,857 | (19.2) | 26,207 | (15.0) | < 0.001 |
Loop diuretics | 45,546 | (12.7) | 20,092 | (11.5) | < 0.001 |
Potassium-sparing diuretics | 9683 | (2.7) | 4892 | (2.8) | 0.233 |
Thiazide diuretics | 6455 | (1.8) | 2795 | (1.6) | < 0.001 |
Vasodilators | 4304 | (1.2) | 1048 | (0.6) | < 0.001 |
Healthcare utilization, mean (± SD) | |||||
Mean number of outpatient visits | 16.8 | (± 15.9) | 17 | (± 14.6) | < 0.001 |
Mean number of inpatient visits | 1.3 | (± 0.7) | 1.4 | (± 0.9) | < 0.001 |
Patient characteristics after matching
Patient characteristics after PS matching | DPP-4 inhibitors | GLP-1 agonists | Std-diff %a | ||
---|---|---|---|---|---|
(n = 160,803) | (n = 160,803) | ||||
Mean age, years (± SD) | 52.7 | (± 10.9) | 53.0 | (± 10.2) | − 0.01 |
Sex, n (%) | |||||
Male | 71,879 | (44.7) | 70,914 | (44.1) | − 0.02 |
Female | 88,924 | (55.3) | 89,889 | (55.9) | |
Comorbidities, n (%) | |||||
Asthma | 10,291 | (6.4) | 10,291 | (6.4) | 0.00 |
COPD | 6432 | (4.0) | 6593 | (4.1) | − 0.01 |
CKD | 4342 | (2.7) | 4663 | (2.9) | − 0.02 |
Ischemic heart disease | 19,457 | (12.1) | 20,100 | (12.5) | − 0.01 |
Depression | 7397 | (4.6) | 7558 | (4.7) | 0.01 |
Hypoglycemia | 4985 | (3.1) | 5146 | (3.2) | 0.01 |
Hyperlipidemia | 92,301 | (57.4) | 91,336 | (56.8) | 0.00 |
Cancer | 9809 | (6.1) | 10,291 | (6.4) | − 0.01 |
Hypertension | 95,839 | (59.6) | 95,678 | (59.5) | 0.00 |
Use of other diabetes medications, n (%) | |||||
Metformin | 100,019 | (62.2) | 99,698 | (62.0) | 0.01 |
TZD | 39,236 | (24.4) | 39,397 | (24.5) | 0.00 |
α-Glucosidase inhibitors | 804 | (0.5) | 804 | (0.5) | 0.00 |
Insulin | 28,141 | (17.5) | 29,749 | (18.5) | − 0.03 |
Meglitinides | 3698 | (2.3) | 3698 | (2.3) | 0.00 |
Use of other medications, n (%) | |||||
ACE inhibitors | 53,226 | (33.1) | 53,065 | (33.0) | 0.00 |
Aldosterone receptor antagonists | 3859 | (2.4) | 4020 | (2.5) | − 0.01 |
α-Blockers | 6915 | (4.3) | 7075 | (4.4) | − 0.01 |
Angiotensin-receptor blockers | 23,638 | (14.7) | 23,638 | (14.7) | 0.00 |
β-Blockers | 36,181 | (22.5) | 36,985 | (23.0) | − 0.01 |
Calcium-channel blockers | 23,799 | (14.8) | 23,960 | (14.9) | − 0.01 |
Loop diuretics | 16,402 | (10.2) | 17,367 | (10.8) | − 0.01 |
Potassium-sparing diuretics | 4181 | (2.6) | 4181 | (2.6) | − 0.01 |
Thiazide diuretics | 2412 | (1.5) | 2412 | (1.5) | 0.00 |
Vasodilators | 965 | (0.6) | 965 | (0.6) | 0.00 |
Healthcare utilization, mean (± SD) | |||||
Mean number of inpatient visits | 1.4 | (± 0.9) | 1.3 | (± 0.7) | − 0.09 |
Mean number of outpatient visits | 15.5 | (± 14.5) | 16.8 | (± 14.5) | − 0.10 |
Incident heart failure hospitalization
Cohort | Medications | No. of patients | Person-years | No. of HF events | Crude incidence per 1000 person-years |
---|---|---|---|---|---|
Overall (primary analysis) | DPP-4 inhibitors | 160,803 | 76,749 | 5714 | 74 |
GLP-1 agonists | 160,803 | 70,469 | 6098 | 87 | |
Baseline HF | |||||
Absent | DPP-4 inhibitors | 158,543 | 75,545 | 5533 | 73 |
GLP-1 agonists | 158,543 | 69,682 | 5870 | 84 | |
Present | DPP-4 inhibitors | 1937 | 686 | 194 | 283 |
GLP-1 agonists | 1937 | 739 | 212 | 287 | |
Baseline CVD | |||||
Absent | DPP-4 inhibitors | 132,047 | 62,552 | 3204 | 51 |
GLP-1 agonists | 132,047 | 58,366 | 3487 | 60 | |
Present | DPP-4 inhibitors | 28,085 | 13,544 | 2579 | 190 |
GLP-1 agonists | 28,085 | 11,835 | 2579 | 218 | |
Individual drugs | |||||
Saxagliptin | Saxagliptin | 49,214 | 19,302 | 1335 | 69 |
GLP-1 agonists | 49,214 | 20,741 | 2058 | 99 | |
Sitagliptin | Sitagliptin | 160,609 | 81,573 | 6108 | 75 |
GLP-1 agonists | 160,609 | 70,441 | 6239 | 89 |
Sensitivity and subgroup analyses
Study population | Medications | Person-years | No. of HF events | Crude incidence (per 1000 person-years) | Adjusted HR of HF (95% CI) | |
---|---|---|---|---|---|---|
Primary diagnosis only | DPP-4 inhibitors | 77,070 | 3107 | 40 | 0.84 (0.80, 0.89) | |
GLP-1 agonists | 70,706 | 3424 | 48 | Reference | ||
Extend follow-up to 45 days | DPP-4 inhibitors | 94,201 | 5714 | 61 | 0.89 (0.85, 0.92) | |
GLP-1 agonists | 89,315 | 6098 | 68 | Reference |